POS0438 IDENTIFICATION OF THREE AUTOPHAGY-RELATED HUB BIOMARKERS OF ANKYLOSING SPONDYLITIS VIA BIOINFORMATICS ANALYSIS OF RNA SEQUENCING DATA OF MACROPHAGES
Authors: Y. Liang, Y. Jiang, W. Weng, J. Chen, X. Luo, J. Gu
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Autophagy is associated with the occurrence and progression of a variety of diseases, such as cancers, cardiovascular diseases, and autoimmune diseases. Ankylosing spondylitis (AS) is a chronic inflammatory disease. Its pathological feature includes local infiltration of inflammatory cells among which macrophages play a dominant role [1]. Currently, previous studies have confirmed that autophagy may be involved in the occurrence and development of autoimmune diseases, such as AS [2]. However, there are few articles discussing which molecule plays a key role in the progress of autophagy of macrophage in patient with AS. <h3>Objectives</h3> This study aimed to detect gene expression in macrophages that originated from peripheral blood mononuclear cells (PBMC) in patients with AS by RNA sequencing (RNA seq) technology, and to identify underlying autophagy-related genes of AS by bioinformatics analysis. <h3>Methods</h3> Peripheral blood mononuclear cells (PBMC) from 4 cases of AS and 4 cases of healthy control (HC) from were isolated and differentiated into M1 macrophages. These cells were then sent to BGI company for RNA seq. Then, Gene Set Enrichment Analysis (GSEA) enrichment analysis, screening of differentially expressed genes (DEGs), Gene Ontology (GO) function annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were conducted. Protein-Protein Interaction (PPI) network of DEGs was constructed, and cluster association analysis was performed by MOCDE plug-in in ctyoscape software. Human autophagy-related genes were downloaded from Human Autophagy Database (HADb). Finally, we took the intersected of human autophagy-related genes and those involved in the top 5 clusters by cluster association analysis. <h3>Results</h3> 1467 DEGs were identified by DESeq2 package in R. Among them, 384 genes were significantly up-regulated while 1083 genes were significantly down-regulated. GO and KEGG enrichment analysis of DEGs revealed several terms related to cell cycle. GSEA analysis of all sequencing data revealed a number of terms related to cell cycle and lysosomes. The PPI network of 1467 DEGs was constructed by using STRING database, and 45 clusters were obtained by using MOCDE plug-in of cytoscape software for cluster association analysis. The intersection of genes involved in the top 5 clusters and 219 autophagy-related genes downloaded from HADb were conducted to obtain 3 autophagy-related genes of AS, which were <i>BIRC5</i>, <i>TP53</i> and <i>CTSB</i>. <h3>Conclusion</h3> Through RNA seq and bioinformatics analysis, we identified 3 potential autophagy-related genes of AS. <i>BIRC5</i>, <i>TP53</i> and <i>CTSB</i> may inhibit the occurrence and development of AS by regulating autophagy. <h3>References</h3> [1]Baeten D, Kruithof E, De Rycke L, et al. Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy. Arthritis Res Ther. 2005;7(2):R359-69. [2]Ciccia F, Haroon N. Autophagy in the pathogenesis of ankylosing spondylitis. Clin Rheumatol. 2016 Jun;35(6):1433-6. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.